Leptin suppresses development of GLP-1 inputs to the paraventricular nucleus of the hypothalamus.

ELife
Jessica E BiddingerRichard B Simerly

Abstract

The nucleus of the solitary tract (NTS) is critical for the central integration of signals from visceral organs and contains preproglucagon (PPG) neurons, which express leptin receptors in the mouse and send direct projections to the paraventricular nucleus of the hypothalamus (PVH). Here, we visualized projections of PPG neurons in leptin-deficient Lepob/ob mice and found that projections from PPG neurons are elevated compared with controls, and PPG projections were normalized by targeted rescue of leptin receptors in LepRbTB/TB mice, which lack functional neuronal leptin receptors. Moreover, Lepob/ob and LepRbTB/TB mice displayed increased levels of neuronal activation in the PVH following vagal stimulation, and whole-cell patch recordings of GLP-1 receptor-expressing PVH neurons revealed enhanced excitatory neurotransmission, suggesting that leptin acts cell autonomously to suppress representation of excitatory afferents from PPG neurons, thereby diminishing the impact of visceral sensory information on GLP-1 receptor-expressing neurons in the PVH.

References

Sep 1, 1990·Developmental Psychobiology·E ThielsC P Cramer
Aug 1, 1988·The Journal of Comparative Neurology·E T Cunningham, P E Sawchenko
Jan 14, 1994·Brain Research. Developmental Brain Research·L RinamanJ G Verbalis
Jun 11, 1999·The American Journal of Physiology·G J SchwartzT H Moran
Jun 9, 2000·Annual Review of Physiology·R S Ahima, J S Flier
Mar 19, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sebastien G BouretRichard B Simerly
Apr 6, 2004·Science·Sebastien G BouretRichard B Simerly
Oct 6, 2006·Obesity·Rebecca L LeshanMartin G Myers
Apr 8, 2009·The Journal of Comparative Neurology·Michael M ScottJoel K Elmquist
Oct 20, 2009·Frontiers in Neuroendocrinology·Harvey J Grill
Jan 8, 2011·European Journal of Pharmacology·Christian D RichardMalcolm J Low
Apr 19, 2011·Physiology & Behavior·Linda RinamanThomas J Koehnle
May 25, 2011·The Journal of Clinical Investigation·Michael M ScottJoel K Elmquist
Jan 27, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sebastien G BouretRichard B Simerly
Feb 14, 2012·The Journal of Clinical Investigation·Eric D BerglundJoel K Elmquist
Nov 16, 2012·Nature·Martin G Myers, David P Olson
Dec 15, 2012·The Journal of Comparative Neurology·Guibao GuJoseph S Heilig
Jan 11, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Karine Bouyer, Richard B Simerly
May 7, 2013·Annual Review of Nutrition·Gary J Schwartz, Lori M Zeltser
Sep 27, 2013·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Edward A FoxJennifer McAdams
Aug 1, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·James W ManiscalcoLinda Rinaman
Aug 21, 2015·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Stefan Trapp, Simon C Cork
Sep 27, 2015·Frontiers in Neuroendocrinology·Amanda E Elson, Richard B Simerly
Apr 1, 2016·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Scott E KanoskiKarolina P Skibicka
May 31, 2016·Cell·Erika K WilliamsStephen D Liberles

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Citations

Jun 24, 2021·Nature Metabolism·Martin G MyersMichael W Schwartz
Jun 30, 2021·British Journal of Pharmacology·Daniel I Brierley, Guillaume de Lartigue
Sep 15, 2021·British Journal of Pharmacology·Anita KabahiziKevin W Williams

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